Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, 200025, Shanghai, China.
Department of Gynecology and Obstetrics, Reproductive Medical Center, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, 197 Ruijin 2nd Road, 200025, Shanghai, China.
Reprod Biol Endocrinol. 2021 May 20;19(1):75. doi: 10.1186/s12958-021-00760-x.
Increasing evidence supports a relationship between obesity and either infertility or subfertility in women. Most previous omics studies were focused on determining if the serum and follicular fluid expression profiles of subjects afflicted with both obesity-related infertility and polycystic ovary syndrome (PCOS) are different than those in normal healthy controls. As granulosa cells (GCs) are essential for oocyte development and fertility, we determined here if the protein expression profiles in the GCs from obese subjects are different than those in their normal-weight counterpart.
GC samples were collected from obese female subjects (n = 14) and normal-weight female subjects (n = 12) who were infertile and underwent in vitro fertilization (IVF) treatment due to tubal pathology. A quantitative approach including tandem mass tag labeling and liquid chromatography tandem mass spectrometry (TMT) was employed to identify differentially expressed proteins. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then conducted to interrogate the functions and pathways of identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in both groups.
A total of 228 differentially expressed proteins were noted, including 138 that were upregulated whereas 90 others were downregulated. Significant pathways and GO terms associated with protein expression changes were also identified, especially within the mitochondrial electron transport chain. The levels of free fatty acids in both the serum and follicular fluid of obese subjects were significantly higher than those in matched normal-weight subjects.
In GCs obtained from obese subjects, their mitochondria were damaged and the endoplasmic reticulum stress response was accompanied by dysregulated hormonal synthesis whereas none of these changes occurred in normal-weight subjects. These alterations may be related to the high FFA and TG levels detected in human follicular fluid.
越来越多的证据支持肥胖与女性不孕或不育之间存在关系。大多数先前的组学研究都集中在确定患有肥胖相关不孕和多囊卵巢综合征（PCOS）的受试者的血清和卵泡液表达谱是否与正常健康对照不同。由于颗粒细胞（GCs）对卵母细胞发育和生育至关重要，我们在这里确定肥胖受试者的 GCs 中的蛋白质表达谱是否与正常体重受试者的不同。
从因输卵管病变而接受体外受精（IVF）治疗的肥胖女性受试者（n=14）和正常体重女性受试者（n=12）中收集 GC 样本。采用包括串联质量标签标记和液相色谱串联质谱（TMT）的定量方法来鉴定差异表达的蛋白质。然后进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，以探究鉴定出的蛋白质的功能和途径。还分析了两组的临床、激素和生化参数。
共发现 228 个差异表达的蛋白质，其中 138 个上调，90 个下调。还确定了与蛋白质表达变化相关的显著途径和 GO 术语，尤其是在线粒体电子传递链中。与正常体重受试者相比，肥胖受试者的血清和卵泡液中的游离脂肪酸水平明显更高。
在肥胖受试者的 GC 中，其线粒体受损，内质网应激反应伴随着激素合成失调，而在正常体重受试者中则没有发生这些变化。这些变化可能与在人类卵泡液中检测到的高 FFA 和 TG 水平有关。
